The polyethylene glycol is an extremely versatile polyether high molecular weight compounds, it can be used in many fields such as medicine, health, food, chemical, etc. Polyethylene glycol can be dissolved in water and many solvents and the polymer has excellent biocompatibility, can be dissolved in tissue fluid in vivo, can be rapidly excreted from the body without any toxic side effects.
In application of polyethylene glycol, end group plays a decisive role, different end groups of the polyethylene glycol has a different use. The polyethylene glycol polymeric chain segment is not limited to the terminal hydroxyl group, polyethylene glycol active derivative obtained through the introduction of other functionalized end groups such as amino, carboxyl, aldehyde group and the like, can greatly broaden the range of applications of polyethylene glycol, making it has a broad application prospect in organic synthesis, peptide synthesis, polymer synthesis and sustained release or controlled release of drugs, targeting administration, etc.
Polyethylene glycol (PEG) active derivative has been reported in many document. The U.S. Pat. No. 5,672,662 described the preparation of linear PEG propionic acid and linear PEG butyric acid, and N-hydroxy succinimide esters thereof. The U.S. Pat. No. described a u-shaped structure of PEG derivative.
Azide not only have important physiological activity, such as azido nucleotides (AZT), is a preferred drug available for treatment of AIDS currently, but also have a wide range of reaction activity, as can be reduced to the amino, can occur 1,3-dipolar cyclo addition reaction with an alkyne, can occur Curtius reaction. Azido-terminated polymer obtained by reducing terminal azido group as a polymeric carrier plays an important role in the liquid phase synthesis of peptide.
Patent document WO 2011075953 A1 describes a novel multi-arm polyethylene glycol having different type of active groups, which formed by the polymerization of ethylene oxide, and an oligomeric pentaerythritol as the initiator. The active end group is selected from the group consisting of hydroxyl, amino, sulfhydryl, carboxyl, ester group, aldehyde group, acrylic and maleic imide group, it does not disclose active end group may be azido group.
Non-patent document “synthesis and characterization of azido-terminated polyethylene glycol” (Xiaohong Wang et. al., Acta Polymerica Sinica, June 2000, issue 3) discloses a synthesis method of a high molecular weight azido-terminated polyethylene glycol, however, the prepared polymer is a linear polyethylene glycol, and only loaded with azido groups, and can not be introduced into the other active groups.
To overcome the deficiencies of the prior art, the present invention provides a multi-arm polyethylene glycol-azido active derivative.